Molecules for regulating cell death

Abstract

The present invention provides compounds capable of regulating apoptosis, e.g., via regulating mitochondrial fission or fusion. The present invention also provides methods of screening for compounds capable of regulating apoptosis and methods of treating conditions association with apoptosis.

What is claimed is: 
     
       1. A method of inhibiting mitochondrial fission in mammalian cells comprising contacting the cells with a compound of the general formula: 
       
         
           
           
               
               
           
         
         wherein R 1  is independently H; a C1-C18 alkyl or C1-C18 heteroalkyl, which may be branched, may be substituted, or combinations thereof; a C1-C18 alkenyl or C1-C18heteroalkenyl, which may be branched, may be substituted, or combinations thereof; a C1-C18alkynyl or C1-C18 heteroalkynyl, which may be branched, may be substituted, or combinations thereof; a C3-C18 aryl or C3-C18 heteroaryl, which may contain a bridge, may be substituted, or combinations thereof; or a C5-C18 cycloalkyl or C5-C18 heterocycle, which may contain a bridge, may be substituted, or combinations thereof; 
         R 2  is H; a C1-C18 alkyl or C1-C18 heteroalkyl, which may be branched, may be substituted, or combinations thereof; or a halogen; 
         R 3  is H; a C1-C18 alkyl or C1-C18 heteroalkyl, which may be branched, or may be substituted, or combinations thereof; 
         R 4  is a halogen; and 
         R 5  is a halogen, 
         thereby inhibiting mitochondrial fission in the mammalian cells. 
       
     
     
       2. The method of  claim 1 , wherein R 3  is a C1 heteroalkyl. 
     
     
       3. The method of  claim 1 , wherein R 3  is a C3 heteroalkyl. 
     
     
       4. The method of  claim 2 , wherein R 2  is H. 
     
     
       5. The method of  claim 3 , wherein R 2  is H. 
     
     
       6. The method of  claim 3 , wherein R 1  is independently selected from H or a C1-C18 alkyl. 
     
     
       7. The method of  claim 4 , wherein R 1  is H. 
     
     
       8. The method of  claim 4 , wherein R 1  is a C1 alkyl. 
     
     
       9. The method of  claim 5 , wherein R 1  is H. 
     
     
       10. The method of  claim 4 , wherein the compound is defined by the structure: 
       
         
           
           
               
               
           
         
       
     
     
       11. A method of inhibiting mitochondrial fission in mammalian cells comprising contacting the cells with a compound defined as 2-mercapto-3-(2-(trifluoromethyl)phenyl)quinazolin-4(3H)one, thereby inhibiting mitochondrial fission in the mammalian cells. 
     
     
       12. A method of inhibiting apoptosis in cells comprising contacting the cells with a compound of the general formula: 
       
         
           
           
               
               
           
         
         wherein R 1  is independently H; a C1-C18 alkyl or C1-C18 heteroalkyl, which may be branched, may be substituted, or combinations thereof; a C1-C18 alkenyl or C1-C18heteroalkenyl, which may be branched, may be substituted, or combinations thereof; a C1-C 18alkynyl or C1-C18 heteroalkynyl, which may be branched, may be substituted, or combinations thereof; a C3-C18 aryl or C3-C18 heteroaryl, which may contain a bridge, may be substituted, or combinations thereof; or a C5-C18 cycloalkyl or C5-C18 heterocycle, which may contain a bridge, may be substituted, or combinations thereof; 
         R 2  is H; a C1-C18 alkyl or C1-C18 heteroalkyl, which may be branched, may be substituted, or combinations thereof; or a halogen; 
         R 3  is H; a C1-C18 alkyl or C1-C18 heteroalkyl, which may be branched, or may be substituted, or combinations thereof; 
         R 4  is a halogen; and 
         R 5  is a halogen, 
         thereby inhibiting apoptosis in the cells.